This invention relates generally to an apparatus and method for rapidly determining the characteristics of an array of diverse materials which have been created on a surface of a substrate, and in particular, to an apparatus and method for rapidly determining the characteristics of a library of diverse materials using high energy electromagnetic radiation.
Combinatorial material science refers generally to methods for creating a collection of chemically diverse compounds or materials and to methods for rapidly testing or screening this library of compounds or materials for desirable characteristics or properties. The combinatorial technique, which was introduced to the pharmaceutical industry in the late 1980s, has dramatically sped up the drug discovery process. Recently, combinatorial techniques have been applied to the synthesis of inorganic materials. Using various surface deposition techniques, masking strategies or processing conditions, it is possible to generate hundreds or thousands of materials with distinct compositions per square inch in an array of elements which form a library. The materials generated using these combinatorial techniques have included high temperature superconductors, magnetoresistors, phosphors and pigments. The discovery of new catalysts should also benefit from these combinatorial techniques. General combinatorial material science methodologies are disclosed, for example, in U.S. Pat. No. 5,776,359 which is incorporated herein by reference.
The problem is that, although these libraries of hundreds or thousands of new potential materials have been generated, these libraries need to be screened for performance characteristics or properties and conventional screening techniques are not sufficiently fast. Another problem for conventional characterization techniques is the low concentration of components in each element of the library. It is therefore necessary to be able to accurately measure these low concentration levels.
In general, x-ray scattering is a well known characterization technique. In addition, the various pieces of an x-ray scattering apparatus are well known. For example, U.S. Pat. Nos. 5,757,882, 5,646,976 and 5163078 describe a multilayer mirror being used in an x-ray beamline. The use of flat glass mirrors for x-ray optics is disclosed in Franks, A., British Journal of Applied Physics., Volume 9, page 349 (1958) and Milch, J. R., Journal of Applied Cryst., Volume 16, page 198 (1983). X-ray beamlines with rotating anode sources and two flat glass mirrors are disclosed in Milch, J. R., Journal of Applied Cryst., Volume 16, page 198 (1983) and Hajduk, D. A., Morphological Transitions in Block Copolymers, Ph.D. dissertation, Princeton University (1994). In addition, x-ray detectors, such as multiwire area detectors (See U.S. Pat. Nos. 3,911,279 and 4,076,981) and CCD-based detectors with integral memories (See U.S. Pat. No. 5,629,524) are known. Many x-ray detectors have also been described in various journals and other publications including Gruner, S. M., Curr. Op. Struct. Biol. 1994, 4, 765; Gruner, S. M., Rev. Sci. Inst. 1989, 60, 1545; Ilinson, N. M., Nucl. Inst. Methods Phys. Res. 1989, A275,587; and Eikenberry E. F. et al., xe2x80x9cX-Ray Detectors: Comparison of Film, Storage Phosphors and CCD Detectorsxe2x80x9d in Morgan, ed. Photoelectric Image Devices Bristol: Inst. of Physics Conf. Ser. No. 121, Institute of Physics 1992, 273.
One conventional technique for structural characterization is x-ray scattering. In this technique, a monochromatic, collimated x-ray beam illuminates a material of interest, and the spatial distribution of the scattered radiation is analyzed to provide information on the structure, dimensions, and degree of ordering of the specimen. Low concentrations of strongly scattering constituent atoms or substructures may also be detected and quantified by this technique. Similar results may be obtained by analyzing the distribution of photon energies scattered into a fixed region of space from a polychromatic x-ray beam. Although the low photon flux and brilliance characteristic of commercially available instruments is acceptable for measurements of individual samples, it is of limited value for combinatorial materials science work. Typical measurements on conventional sources require at least fifteen minutes per specimen, implying at least 24 hours to characterize a 96-element library. Obviously, the total screening time will increase dramatically as the total number of elements increases. Therefore, it is desirable to provide an apparatus and method for characterizing libraries of different materials using x-ray scattering to solve the above problems associated with conventional systems and techniques. It is to this end that the present invention is directed.
An apparatus and method for characterizing a library of different materials using x-ray scattering in accordance with the invention provides numerous advantages over conventional characterization apparatus. For example, compared to conventional instruments, the apparatus advantageously delivers both a higher total photon flux and a higher flux per unit area to each library element. This reduces the time required to analyze each element thereby reducing the total time needed for library characterization. It also reduces the time required for calibration of the instrument as described below. The light generated by such an intense beam when it strikes a phosphorescent screen is easily detected by the eye which facilitates alignment of the instrument prior to the measurement. The apparatus also has a modular sample stage which supports and moves a library containing a plurality of elements so that the plurality of elements may be tested more rapidly than with conventional apparatus. The apparatus in accordance with the invention may perform spatial scanning so that arrays and libraries of materials may be rapidly analyzed and characterized. The positioning of the library in relation to the x-ray beam may be computer controlled so that the apparatus may automatically characterize and analyze each element on the library by moving the library a predetermined distance. This automatic movement of the library relative to the x-ray beam eliminates human error and avoids having a human reposition the library after each element is characterized.
In accordance with another aspect of the invention, a method for preparing a library of materials for characterization and analysis by the x-ray apparatus is provided. The library may be prepared several different ways. In the embodiments below, samples which are powders are being used, but the library preparation method may be used with other types of samples. In a first embodiment, a plate having a predetermined thickness may have an array of holes drilled through the plate. The holes may be sealed at one end with a chemically inert material which is nearly transparent to x-rays of the appropriate wavelength and that does not generate appreciable x-ray scattering in the angular regime of interest. Suitable materials may include poly(imide) (Kapton(trademark)), poly(ethylene terephthalate) (Mylar(trademark)), thin aluminum foils and thin beryllium foils. Once the different materials have been deposited into the appropriate hole, the open ends of the holes may be sealed with the same material. The library is now ready for characterization using the x-ray apparatus. In a second embodiment, the same metal plate with a first end covered by the plastic material may be used and then the powders to be placed in each hole may be suspended in a non-solvent liquid with a low vapor pressure and deposited in the appropriate holes using a liquid handling robot. During the loading process, the plate may be heated to promote evaporation of the non-solvent liquid and the other end of the holes may be sealed with the same plastic which leaves the powder in the hole for characterization. In a third embodiment, the sample powders may be blended with a viscous, non-solvent binder and each sample may be deposited onto a piece of the plastic film. Once the elements are dried, the plastic film may be mounted on an aluminum frame to provide mechanical support and strength to the film which contains the dried elements.
In a fourth embodiment of the library preparation method, the first ends of the holes in the same metal plate are blocked by a sheet of material, and the wells thus formed are filled by a solution of the materials of interest in a volatile solvent. The blocking material is chosen so as to be nonreactive with respect to the solution of interest and to be insoluble in the solvent. The blocking material may therefore include fluorinated polymers such as Teflon(trademark), poly(imide) or metals. The solvent is removed by air drying, by vacuum drying or by exposure to an oxygen-free environment followed by gentle heating in a vacuum. Once of the solvent has been removed, the remaining materials of interest may form a film which completely fills and remains in each wells so that the blocking material may be removed. If the remaining materials of interest do not form a film with sufficient mechanical strength to remain in the wells when the blocking material is removed, the blocking material must be made from a material that is substantially transparent to x-rays as described above. Suitable materials may include poly(imide) (Kapton(trademark), poly(ethylene terephthalate) (Mylar(trademark)), thin aluminum foils and thin beryllium foils.
Thus, in accordance with the invention, an apparatus for characterizing a library is provided in which the library contains an array of elements, each element contains either a chemically distinct combinations of materials, or a chemical composition which may be identical to that existing elsewhere on the library but has been subject to distinct processing conditions. The apparatus comprises an x-ray beam directed at the library, a chamber which houses the library, and a beamline for directing the x-ray beam to illuminate a region on the library in the chamber. The chamber further comprises a translation stage that holds the library and that is programmable to change the position of the library relative to the x-ray beam and a controller that controls the movement of the translation stage to expose each element to the x-ray beam in order to rapidly characterize each element in the library.
In accordance with another aspect of the invention, a method for characterizing a library is provided in which the library contains an array of elements, each element contains either a chemically distinct combinations of materials, or a chemical composition which may be identical to that existing elsewhere on the library but has been subject to distinct processing conditions. The method comprises directing an x-ray beam generated by an x-ray source towards the library housed within a chamber and moving the library in a predetermined manner to expose each element of the library separately to the x-ray beam in order to rapidly characterize each element in the library.
In accordance with another aspect of the invention, an apparatus for characterizing a library is provided in which the library contains an array of elements and each element contains either a chemically distinct combinations of materials, or a chemical composition which may be identical to that existing elsewhere on the library but has been subject to distinct processing conditions. The apparatus comprises means for generating an x-ray beam which is directed towards the library, a chamber which houses the library and means for directing the x-ray beam onto the library in the chamber. The chamber further comprises means for holding the library, means for changing the position of the library relative to the x-ray beam and means for controlling the movement of the translation stage to expose each element to the x-ray beam in order to rapidly characterize each element in the library.
In accordance with yet another aspect of the invention, a method for preparing a library is provided in which the library contains an array of elements and each element contains either a chemically distinct combinations of materials, or a chemical composition which may be identical to that existing elsewhere on the library but has been subject to distinct processing conditions. The method comprises forming an array of holes from a first side of a plate through to a second side of the plate, sealing a first side of the plate with a film to form wells in the plate, depositing a predetermined amount of one or more materials into each well of the plate, and sealing the second side of the plate with a second piece of film to trap the deposited one or materials in each of the wells in the plate so that a beam may impinge upon each element containing the one or materials and characterize the elements of the library.
In accordance with yet another aspect of the invention, a method for preparing a library is provided in which the library contains an array of elements and each element contains either a chemically distinct combinations of materials, or a chemical composition which may be identical to that existing elsewhere on the library but has been subject to distinct processing conditions. The method comprises forming one or more deposition compounds, each deposition compound comprising one or more materials blended into a viscous, non-solvent liquid, depositing the deposition compounds onto a sheet of film at predetermined locations to form an array of elements, drying the deposition compounds onto the film to form a library of one or more materials, and mounting the firm with the dried deposition compounds onto a frame to provide support to the plastic film so that the deposition compounds may be rapidly characterized.
In accordance with still another aspect of the invention a method for preparing a library is provided in which the library contains an array of elements and each element contains either a chemically distinct combinations of materials, or a chemical composition which may be identical to that existing elsewhere on the library but has been subject to distinct processing conditions. The method comprises blocking the first ends of holes in a metal plate with a sheet of material so that the wells thus formed are filled by a solution of the materials of interest in a volatile solvent. The blocking material is chosen so as to be nonreactive with respect to the solution of interest and to be insoluble in the solvent. The solvent is then removed by air drying, by vacuum drying or by exposure to an oxygen-free environment followed by gentle heating in a vacuum. Once of the solvent has been removed, the remaining materials of interest may form a film which completely fills and remains in each wells so that the blocking material may be removed. If the remaining materials of interest do not form a film with sufficient mechanical strength to remain in the wells when the blocking material is removed, the blocking material must be made from a material that is substantially transparent to x-rays as described above.